1. Field of the Invention
The present invention relates to a process for preparing an optically active 2-aminopropanal, which is widely used as a starting material for synthesis of intermediates of drugs, examples of which include an intermediate of bestatin as a carcinostatic, an intermediate of a renin inhibitor as a hypotensor and an intermediate of an HIV protease inhibitor.
2. Description of the Related Art
Two general processes are known for preparing an optically active 2-aminopropanal using an a-amino acid as a starting material. According to one process, an .alpha.-amino acid is reduced to the corresponding .alpha.-amino alcohol, which is then oxidized to the corresponding aldehyde (see Japanese Patent Laid-Open No. 23,4071/1987). According to another process, an .alpha.-amino acid is esterified, and the resulting ester is reduced to the corresponding aldehyde under mild conditions.
In the first-mentioned process comprising reduction of an .alpha.-amino acid to the corresponding .alpha.-amino alcohol and subsequent oxidation thereof to the corresponding aldehyde, a relatively mild oxidation reaction is carried out from the viewpoint of problems of oxidation to an unstable aldehyde and epimerization thereof. Examples of such a mild oxidation reaction include oxidation with chromium oxide-pyridine and oxidation with dimethyl sulfoxide [see Journal of Organic Chemistry, 52, 1487 (1987)]. Further, oxidation with pyridinium dichromate is known. According to any one of these reactions, however, by-product(s) is formed, while there is a possibility that epimerization of the amino group might occur because the liquid systems involved in the reaction and post-treatments are not always neutral.
On the other hand, in the second-mentioned process comprising esterification of an .alpha.-amino acid and subsequent reduction of the resulting ester, a mild reduction reaction is carried out from the viewpoint of reduction to an unstable aldehyde as well. Reduction with diisobutylaluminum hydride may be mentioned as a general mild reduction method (see, for example, Journal of Organic Chemistry, 52, 1487 (1987), wherein an example of synthesis is described).
According to this process as well, however, delicate control of the equivalent number of a reducing agent and a reaction temperature as low as -60.degree. to -78.degree. C. are necessary because reduction of the ester must be terminated just when the aldehyde is formed. Further, this process involves a problem that, even when the equivalent number of the reducing agent is controlled, unreacted matter remains and an alcohol is formed as a result of further reaction. As described hereinabove, an optically active .alpha.-amino aldehyde is one of the aldehydes which are difficult to synthesize, because such an aldehyde is unstable in itself and characteristically subject to epimerization of the amino group thereof at the .alpha.-position because of the influence thereon of the aldehyde group.